Background and purpose: Paediatric low-grade gliomas (pLGG) are the most common brain tumours in children. Radiotherapy, once the standard treatment for unresectable pLGG, is now used less frequently due to concerns about late side effects. The Nordic Society of Paediatric Haematology and Oncology (NOPHO) Radiotherapy Working Group aims to provide consensus guidelines on the use of radiotherapy for pLGG, addressing the current controversies and facilitating decision-making. Patient/material and methods: The guidelines were developed by clinical/radiation oncologists from the Nordic and Baltic countries and two international experts during a 2-day working group meeting. The meeting included presentations from the international experts and was preceded by a survey on radiotherapy practices and a non-systematic review of the literature on pLGG. Results: We present consensus-based recommendations for radiotherapy of pLGG. The guidelines discuss indications and timing of radiotherapy, age-related considerations, and the impact of genetic predisposition disorders such as neurofibromatosis type 1. Modern radiotherapy techniques, such as proton therapy, are highlighted for their potential to reduce long-term side effects. Interpretation: Radiotherapy remains the most effective treatment for unresectable pLGG, but its use must be carefully weighed against the risk of long-term side effects. The guidelines emphasise a personalised treatment approach, considering the evolving field of targeted therapies and the importance of multidisciplinary input in decision-making.

Reirradiation can be considered for some patients with recurrent or second primary head and neck squamous cell carcinoma arising within previously irradiated regions, a clinical scenario associated with few therapeutic options. The increasing use of modern conformal radiotherapy techniques, including intensity-modulated radiotherapy, proton therapy, and stereotactic body radiotherapy, has expanded the feasibility of reirradiation in clinical practice. However, evidence remains heterogeneous, and clinical choices are challenged by substantial variability in patient presentation, previous treatments, and toxicity risk. This international expert consensus statement aims to provide pragmatic guidance across key domains, including patient selection, imaging, target delineation, treatment planning, dose accumulation, and toxicity management. Developed through a structured expert consensus process with formal agreement assessment, this document reflects current expert practice. By offering a shared clinical framework, this consensus seeks to promote more consistent practice, facilitate communication across centres, and support future research efforts in this complex and evolving field.

IntroductionThe performance of knowledge-based autoplanning depends on historical plans used to train the autoplanning models. Here, we investigate the applicability of an existing RapidPlan (RP) model for head and neck cancer to a novel planning and delivery solution (RapidArc Dynamic, RAD), which has the potential to improve plan quality through the integration of new degrees of freedom. RAD integrates static-angle modulated ports and a dynamic collimator in volumetric-modulated arc therapy (VMAT) fields.Materials and methodsA cohort of 48 oropharyngeal cancer (OPC) patients was retrospectively included in the planning study. Organ-at-risk (OAR) sparing was evaluated for VMAT and RAD, respectively, using both a VMAT-based RP model and a RAD-based RP model, resulting in four plans per patient: VMAT (RP-VMAT), VMAT (RP-RAD)), RAD (RP-VMAT) and RAD (RP-RAD). Differences were assessed with the related-samples Friedman’s two-way ANOVA test by ranks, correcting the p value for multiple testing (p ≤ 0.05 considered significant).ResultsFor RAD plans, the RAD-based RP model improved the sparing of all OAR (p ≤ 0.001) except the parotids. However, the RAD plans were at least equivalent to the VMAT plans when optimizing with RP-VMAT, indicating the safety of initially implementing RAD with a VMAT-based RP model. In addition, when optimizing with RP-RAD, all OAR except the trachea were significantly better spared with RAD (RP-RAD) compared to VMAT (RP-RAD) (p = 0.039 for the esophagus and < 0.001 for the remaining OAR), with a median reduction of Dmean by 4.8 Gy and 3.5 Gy, respectively, for the larynx and the constrictor muscle. There was also a significant reduction in the estimated risk of dysphagia (1.9 pp) and acute mucositis (1.3 pp) (p ≤ 0.001).ConclusionsVMAT-based RP models appear to remain applicable for optimization with the novel RAD solution until RAD-specific RP models are developed. Furthermore, RAD shows promise for OPC in terms of sparing of midline OARs.

When reirradiation dose constraints are derived using accumulated dose, the underlying image registrations contribute to the uncertainty. We performed a structure-based evaluation of deformable image registrations, to estimate the uncertainty in previously published dose constraints related to carotid blowout and osteoradionecrosis after head and neck reirradiation.With the workflow of the current analysis, the uncertainty was small in the majority of the cases (<4 Gy in accumulated equivalent dose in 2-Gy fractions), but with substantial outliers resulting from anatomical alterations. Our previously suggested dose constraints appear to be reliable with regard to the underlying image registrations.

Reirradiation (reRT), defined as administering a course of radiation therapy to a specific area previously irradiated, is an evolving treatment strategy for locoregionally recurrent cancer that offers significant potential and poses inherent challenges. Advances in such techniques as intensity-modulated and stereotactic body radiation therapy have improved precision, making reRT a viable option for complex scenarios previously deemed high-risk. Nevertheless, reRT remains associated with substantial risks-including life-threatening side effects, functional impairments, and psychosocial effects-which must be carefully balanced against the patient's overall health and the likelihood of achieving cancer control or palliation. Patient selection is essential to optimize outcomes while mitigating risks. Decisions should account for tumor characteristics at the time of primary diagnosis and recurrence, elapsed time since prior treatment, the possibility of delivering meaningful doses to the tumor, and the cumulative irradiation tolerance of normal tissues. Advanced imaging modalities, such as functional magnetic resonance imaging and fluorine-18-labeled fluorodeoxyglucose-positron emission tomography, are important for distinguishing recurrences from treatment-induced changes, refining treatment targets, and minimizing exposure to healthy tissue. Combined treatment with systemic regimens-targeted therapies and immunotherapy in particular-offers promising opportunities but requires coordination to manage side effects. Standardized guidelines, such as those from the European Society of Therapeutic Radiology and Oncology-European Society for Research and Treatment of Cancer, are essential for improving the consistency of reporting, guiding clinical decision making, and fostering patient-centered care. Multidisciplinary collaboration and ongoing research, particularly through clinical trials, are central to fully exploiting reRT strategies. In addition, the development of innovative techniques, such as proton therapy, would likely enable safer treatments. These efforts aim to improve the therapeutic balance of reRT, enhancing outcomes and quality of life.

Background: In 2015, a proton therapy (PT) facility was established in Sweden with one aim being to ensure access for all children expected to benefit from PT. Despite potential dosimetric advantages and full subsidisation, PT is not always selected. This study explores reasons for choosing alternative radiotherapy (RT) modalities in a paediatric population. Material and methods: RT courses delivered to patients ≤ 18 years during 2016–2023 were identified from a national registry. Medical records were retrospectively reviewed to identify reasons for not selecting PT. Results: Only 34% (n = 275) of all courses identified were delivered with PT. Of the remaining 66% (n = 544), 90% were photon RT, 9% combined PT and photon RT, and 1% electron RT. Among photon RT courses, 97% were delivered with conventional external beam radiotherapy (EBRT), 2% with stereotactic radiotherapy (SRT), and 1% with brachytherapy. The most common reason for choosing photons was non-curative intent (35%), followed by equal or superior expected outcome compared to PT (23%), total body irradiation (TBI) (15%), and uncertainties due to air, organ motion, or metal in field (15%). Dosimetric comparison led to the selection of a favourable or equal photon plan in 8%. Logistical, social, and technical reasons constituted 4%. Conclusion: While PT can reduce radiation exposure to healthy tissues, particularly important in children, clinical, logistical, and technical factors often necessitate alternative RT modalities. This study highlights the importance of individualised RT planning and multidisciplinary collaboration to balance medical, technical, and practical considerations to ensure optimal treatment approach in every child.

A comparison of acute toxicity between photon and proton radiotherapy (RT) for children undergoing treatment for medulloblastoma. This retrospective multi-institutional cohort study included 96 children < 18 years treated for medulloblastoma in Sweden during 2008–2020. Patients treated with protons (n = 37) and photons (n = 59) were compared regarding acute side effects and radiation dose to intracerebral organs at risk (OARs). Data was collected from a prospectively maintained national database and was supplemented from a retrospective review of medical records. Acute symptoms were graded according to CTCAE (Common Terminology Criteria for Adverse Events), maximum grade occurring during RT and within 2 months after RT. Hematological toxicity was evaluated according to maximum grade and percentual reduction during RT. No significant differences in incidence or severity of acute symptoms were observed between proton-RT and photon-RT; grade ≥ 2 fatigue (5.4 vs. 10.2

Objectives Children with midline gliomas have a dismal prognosis and current treatment options cannot offer cure. At progression after primary radiotherapy, reirradiation can be offered to relieve symptoms. The aim of this study is to evaluate the outcome of children treated with reirradiation for midline glioma since implementing national guidelines in 2019. Methods All children reirradiated for midline gliomas 2019-2023 in Sweden were retrospectively analysed. A review of medical records and treatment plans was performed to collect data on clinical and treatment characteristics, severe side effects, treatment effect and survival. Results Eleven patients were analysed and the median age at start of first reirradiation was 9 years (4-18). The median overall survival from end of first reirradiation was 5.6 months. The median follow-up was 4 months (0-14). The most common (91%) treatment at primary irradiation was 54 Gy in 30 fractions and at first (82%) and second (75%) reirradiation it was 20 Gy in 10 fractions. The median time between first and second irradiation was 8 months (4-27) and 6 months (6-7) between second and third irradiation. The median D2% to the brainstem was 74 Gy (59-91) at first reirradiation (n=11) and 95 Gy (77-95) at second reirradiation (n=4). In patients where the indication for reirradiation was progression of symptoms, 6 patients (67%) had relief of symptoms after reirradiation, and 3 patients (75%) had relief of symptoms after re-reirradiation. No patients had grade ≥3 side effects at reirradiation. One patient had acute respiratory grade ≥3 side effect (hyperventilation) at second reirradiation but recovered after treatment with steroids. Conclusion The implementation of national guidelines has harmonised how paediatric midline glioma are treated with reirradiation in Sweden. A structured follow-up shows that severe side effects are rare, and that reirradiation can offer relief of symptoms for selected patients.

Background and purpose: The aim of this study is to validate an Normal Tissue Complication Probability (NTCP) model for xerostomia in a large quality-registry cohort, enabling its future use in individualized NTCP-based treatment planning. Material and methods: A model predicting grade ≥ 2 xerostomia (6 months post-radiotherapy) was selected for validation, including the mean dose to both the parotid and the submandibular glands, in addition to the baseline score for xerostomia, as predictors. Our local validation cohort consisted of 674 patients (204 events), treated between 2012 and 2024, with a median follow-up of 10.3 months (range 5–24). A closed testing procedure was performed to investigate the need for model updating, and the performance of the models was assessed with calibration curves, discrimination, the Brier score, and the Hosmer-Lemeshow test. Results: The calibration curve demonstrated that the model predicted the dose–response relationship well. The validation cohort showed a slightly stronger dose response, with a slope of 1.16. The calibration intercept of −0.12 revealed an overestimation of xerostomia. However, the closed testing procedure indicated that a recalibration of the model was needed, and the HL-test showed a significant deviation. The recalibrated model showed perfect calibration but still limited discrimination (Area Under the Curve (AUC) 0.62). Conclusion: The validated model performed well in our real-life dataset despite the differences between the training and validation cohorts, particularly considering the lack of baseline score in our cohort. This highlights the potential for improved performance with baseline inclusion but still suggests that an individualized NTCP-based treatment-planning protocol can be developed using the recalibrated published model.

Background and purpose: Neuroblastoma is the most common extracranial solid tumour in children. Radiotherapy is commonly part of the multimodal treatment for high-risk patients. The aim of this study is to analyse doses to organs at risk (OAR) in comparative proton and photon treatment plans for children treated for neuroblastoma and report side effects. Patient/material and methods: All children in Sweden treated with curative intent radiotherapy for abdominal neuroblastoma in 2017–2024 with comparative proton and photon treatment plans were retrospectively identified through a national registry (RADTOX), where data on side effects were collected. Doses to OAR were compared in each patient’s proton and photon treatment plans. Results: A total of 30 children with a median age of 45 months (range 11–150) were included. The low-dose spread was significantly lower in the proton compared to the photon treatment plans measured as Body V5Gy and V10Gy (p < 0.001). Furthermore, the mean doses to the bowel bag, kidneys, liver, pancreas, and spleen were significantly lower in the proton plans. The median follow-up was 14 months (1–61), and the 2-year overall survival was 75.3%. While acute radiotherapy related grade ≥ 2 side effects were experienced by 12 patients (40%), late side effects were experienced by 7 patients (13%). The most common side effects were haematological and from the upper gastrointestinal tract. Interpretation: In selected cases, proton treatment can offer lower doses to OAR and less low-dose exposure compared to photon treatment in children treated for abdominal neuroblastoma. Whether this translates into a clinical benefit is currently unclear and should be evaluated in future studies.

Introduction Reirradiation has gained increasing interest, as advances in systemic therapy increase the survival of patients with cancer, and modern radiation techniques allow more precise treatments. However, high-quality prospective evidence on the safety and efficacy of reirradiation to guide clinical practice remains scarce. This systematic review evaluates ongoing prospective studies on reirradiation to identify research gaps and priorities. Methods A systematic review of ClinicalTrials.gov was conducted on July 11, 2024, using search terms related to reirradiation. Inclusion criteria were prospective studies that were “recruiting,” “not yet recruiting,” or “active, not recruiting.” Studies with published results, retrospective, and in-silico studies were excluded. The review followed PRISMA 2020 guidelines and recommendations for systematic searches of clinical trial registries. Results Among 1026 identified studies, 307 were screened, 99 were included. Fourty (40%) focused on central nervous system (CNS), 23 (23%) head and neck, and 17 (17%) on pelvic reirradiation. Most studies (90%) were interventional, with 32 (32%) phase II and 4 (4%) phase III trials. Sixteen trials were randomized (RCTs), including the 4 phase III trials for recurrent glioblastoma, rectal and nasopharyngeal cancer. Ten dose escalation trials focus on recurrent prostate, rectal, and non-small cell lung cancer as well as glioma. Modern high-precision radiotherapy techniques were frequently used, with 21 (21%) studies using stereotactic radiotherapy and 17 (17%) using particle therapy. Combinations with systemic therapies were investigated in 41 (41%) studies. Conclusion Ongoing studies most frequently focus on CNS, head and neck, and pelvic reirradiation. There remains a critical need for RCTs, in particular for lung, breast, and gynecological cancers. Dose escalation trials, application of precision radiation techniques and combinations with modern systemic therapy may help define the optimal multimodality treatment schedules.